Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program


      • We compared varenicline or nicotine replacement therapy for smoking cessation.
      • Oxidative stress and CO were reduced after 3 months in both treatment arms.
      • Arterial wave reflections were similarly reduced after 3 months in both treatment arms.
      • The improvement of endothelial glycocalyx and CO was more evident after varenicline.
      • Vascular function was further improved at 1 year of smoking cessation.


      Background and aims

      The effects of medically-aided smoking cessation on vascular function and oxidative stress are not fully clarified.


      One hundred eighty-eight current smokers were randomized to varenicline or nicotine replacement treatment (NRT) for a 3-month period. We assessed: (a) augmentation index (Aix) and pulse wave velocity (PWV); (b) perfusion boundary region (PBR) of sublingual microvasculature (range:5–25 μm), an index of the endothelial glycocalyx thickness, using Sideview, Darkfield imaging; (c) the exhaled CO; and (d) the malondialdehyde (MDA) and protein carbonyls (PC) plasma levels, as markers of oxidative stress, at baseline and after 3 and 12 months.


      After 3 months of treatment, CO, MDA, PC and Aix were decreased in all subjects (median CO: 25 vs. 6 ppm, MDA: 0.81 vs. 0.63 nmol/L, PC: 0.102, vs. 0.093 nmol/mg protein, Aix: 13% vs. 9%, p < 0.05) while PWV remained unchanged. Endothelial glycocalyx integrity showed a greater improvement in the varenicline than the NRT treatment (PBR range 5–9 μm: 1.07 ± 0.02 vs. 1.17 ± 0.02 μm, p = 0.03) in parallel with the greater CO reduction (5 vs. 7 ppm, p = 0.02). At 1-year follow-up, MDA, PC, Aix and PBR at 5–25 μm range were further improved in subjects who abstained from smoking (n = 84 out of 188), while the above markers and PWV deteriorated in relapsed smokers (p < 0.05).


      A smoking cessation program using varenicline or NRT for 3 months resulted in a decrease of CO, oxidative stress, arterial stiffness and restored endothelial glycocalyx. These effects were more evident after varenicline treatment, likely because of a greater CO reduction, and were maintained after 1 year only in subjects who abstained from smoking.


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